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INTRODUCTION EGF is also speculated to enhance the transformation
of fibroblasts to fibrosarcomas by inducing the
Hepatocellular carcinoma (HCC) is the fifth most development of HCC in transgenic mice. Additionally,
[12]
common cancer and the second leading cause of cancer a functional polymorphism in the EGF gene is reported
deaths all over the world according to the World Health to be associated with the risk of development of
Organization data. In Egypt, incidences of liver cancer HCC. Kannangai et al. reported overexpression of
[1,2]
[13]
[14]
have risen dramatically over the last two decades, and EGFR associated with late-stage HCC, increased cell
now it is the most common cancer in men and the proliferation, and degree of tumor differentiation. All
second most common cancer in women, with an annual these reports support our hypothesis that EGF is a
[3]
rate of HCC development of 1-4%, when hepatitis C virus viable candidate for screening for different cirrhotic
(HCV)-related cirrhosis is established. Patients suffering populations for early detection of HCC. Transarterial
[1]
from HCC unlike most solid tumors are confronted chemoembolization (TACE) being the standard of
with the coexistence of two life-threatening conditions, care treatment for patients with intermediate stage
malignancy and cirrhosis, which makes their prognostic HCC, the best candidates are patients with Child A [1,2]
assessments difficult. Despite the usefulness of clinical cirrhosis. And, multifocal non-invasive HCC was also
staging systems for HCC in routine clinical decision included in the study as an arm to determine the EGF
making [e.g., Barcelona-Clinic Liver Cancer (BCLC) levels in response to the treatment. Most importantly,
algorithm], there is still a need to refine and complement we tried to identify whether circulating EGF levels
outcome predictions. [4] were altered in cirrhotic livers with and without
HCC. The results from the studies showed that EGF
There is an obvious lack of minimally invasive, cost- was indeed a sensitive biomarker indicative of poor
effective, highly sensitive, and specific biomarkers for survival outcome, and it was positively correlated with
accurate diagnosis of HCC independent of the cirrhosis age in the older population.
status. Alpha-fetoprotein (AFP) is not a reliable marker
in early HCC diagnosis due to its low specificity and METHODS
sensitivity, which renders it unsatisfactory and suggests
an urgent need for novel biomarkers for early stage This case-control study was conducted on 151 patients
[5]
HCC detection. Measurement of circulating levels of with chronic liver disease, presented to the Hepatology
angiogenic factors in patients with cancerous tumors Clinic, from June 2010 to June 2011. Four groups of
have several advantages over the direct assessment patients were studied: HCC, chronic hepatitis C with or
of tumor angiogenesis, it does not require a tumor without liver cirrhosis, in addition to a fourth group of
specimen, thus they are theoretically applicable to healthy control subjects with well-matched age and sex.
every cancer patient for their technical simplicity Group I comprised 51 patients with unresectable HCC
and the availability of repeated measurements during (intermediate, advanced, and terminal stages), lesions
(i) initial diagnosis, (ii) course of various anticancer were assessed regarding the number, size, vascular
treatments, and (iii) long after the treatment is over. [6,7] invasion, and distant metastasis. Patients in this group
Vascular endothelial growth factor (VEGF) is well were subdivided according to eligibility for TACE into
known to play a crucial role in tumor angiogenesis two subgroups. Subgroup Ia comprised 21 patients with
by inducing new vessel formation and promoting an intermediate stage HCC, who were eligible for TACE
tumor invasion and metastasis, also VEGF levels are (BCLC stage B). Their EGF levels were assessed before
higher in HCC patients. VEGF is used as a biomarker and 1 week after TACE. Subgroup Ib comprised 30 HCC
of lymph node metastasis in HCC. In addition, the patients who were not eligible for TACE, in advanced and
expression of VEGF is closely correlated with tumor terminal stages (BCLC stages C and D). Group II comprised
recurrence and prognosis. Of note, VEGF receptor 40 chronic hepatitis C patients without cirrhosis. Group
expression levels have also been found to correlate III comprised 40 patients with HCV-related cirrhosis with
with the development of tumor. Epidermal growth no evidence of HCC. Group IV comprised 20 apparently
[8]
factor (EGF), another key regulator of cell survival healthy subjects as a control group with no evidence of
and proliferation, is another biomarker identified in liver disease and/or neoplasm. They were all with well-
the pathogenesis and progression of different types matched age and sex.
[9]
of cancer. During 1980s, several reports described
the overexpression of EGF and EGF receptor (EGFR) All patients were subjected to the following history
in a variety of epithelial tumors, which may have taking, complete physical examination, and routine
a critical role in the etiology of human cancers. [10,11] laboratory biochemical and hematological tests.

Hepatoma Research | Volume 2 | Issue 1 | January 15, 2016 19